Search Results (462)

Background/Objectives: This preliminary pilot case series aims to evaluate the feasibility and temporal evolution of pain and function following an ultrasound-guided infiltration technique with hyaluronic acid and methylprednisolone in a specific patient population with Temporomandibular Disorders (TMD) characterized by MRI-confirmed retrodiscal tissue hyperemia. Given the absence of a control group, this study represents a preliminary exploration of a clinical approach utilizing individualized interocclusal devices during infiltration. Methods: Twenty-eight patients (16 females, 12 males) with TMD and MRI evidence of retrodiscal tissue hyperemia were enrolled in this prospective, uncontrolled study. A unique protocol was employed, utilizing individualized interocclusal devices to optimize joint space access during bilateral ultrasound-guided infiltration of a mixture containing low-molecular-weight hyaluronic acid, lidocaine, and methylprednisolone acetate. Pain intensity (VAS 0–100 mm) and associated symptoms (tinnitus, vertigo, headache, joint clicking) were assessed at baseline and at 30, 60, and 90 days’ follow-up. Results: A statistically significant temporal reduction in pain was observed at all follow-up points (p < 0.001), with the mean VAS score decreasing from 70.5 ± 11.4 mm at baseline to 43.0 ± 11.1 mm at 90 days. Joint clicking disappeared in 80% of patients immediately after treatment. Conclusions: The ultrasound-guided infiltration technique, combined with personalized interocclusal support, demonstrated preliminary feasibility and short-term temporal improvement in pain and joint clicking in this specific patient cohort. Due to the lack of a control group and the multimodal nature of the intervention, these findings should be considered preliminary and do not allow for causal inferences regarding the efficacy of individual components. Full article

Background/Objectives: Tinnitus is a prevalent auditory condition associated with significant psychological burden and limited treatment efficacy. While physical activity confers broad health benefits, its relationship with tinnitus remains understudied. This study examined associations between domain-specific physical activity and tinnitus in a nationally representative sample of U.S. adults. Methods: Data from NHANES 2015–2018 were analyzed. The final analytic sample comprised 4301 adults aged 20 years and older. Tinnitus was assessed via the NHANES audiometry questionnaire. Physical activity was categorized as low, moderate, and high (MET-min/week) separately for work-related (WORK) and non-work-related (NW) domains. Survey-weighted multivariable logistic regression models, adjusted for age, sex, race, BMI, poverty–income ratio, sedentary time, smoking, education, noise exposure, hypertension, diabetes, and depressive symptoms, were used to examine associations. Linear trends across ordered physical activity categories were evaluated using ordinal trend analyses. Results: The weighted prevalence of tinnitus was 17.3%. High NW physical activity (PA) was associated with significantly lower odds of tinnitus (OR = 0.70, 95% CI: 0.488–0.995, p = 0.0475), while high WORK PA was associated with significantly higher odds (OR = 1.30, 95% CI: 1.06–1.60, p = 0.018). Trend analyses confirmed opposing linear trends across ordered categories: inverse for NW PA (OR = 0.83 per category, p-trend = 0.0406) and positive for WORK PA (OR = 1.14 per category, p-trend = 0.017). Noise exposure and depressive symptoms were independently associated with tinnitus across both models. Conclusions: These findings suggest a domain-specific paradox: NW PA was associated with lower odds of tinnitus, whereas WORK PA was associated with higher odds. These results highlight the importance of domain-specific assessment and identify recreational activity as a potential modifiable factor warranting further investigation. Given the cross-sectional design, these associations should not be interpreted as causal. Full article

Driven by the digital transformation of territorial spatial governance, traditional urban planning is irreversibly shifting towards a data-driven empirical paradigm. However, constrained by mimetic isomorphism and path dependence, many geography-based regional universities remain trapped in an educational dilemma: they overemphasize morphological representation while marginalizing quantitative decision-making, fostering a structural mismatch between graduate competencies and industry demands. To explore a systematic pathway out of this dilemma, this study chronicles a three-year pedagogical intervention utilizing a mixed-methods design with a historical control cohort (N = 275) within the urban planning program of Gansu Agricultural University—a regional institution situated in a less-developed frontier where territorial renewal demands macro-spatial synthesis over aesthetic forms. The intervention strategically redefined the graduate competency profile as “spatial data analysts”, constructing a pedagogical model comprising foundational algorithmic training, cross-disciplinary faculty collaboration, and real-world Project-Based Learning (PBL), coupled with a restructured, evidence-based evaluation system. Longitudinal tracking and quantitative analyses indicate a structural alignment with elevated educational efficacy. At the macro level of employment trajectories, the proportion of graduates securing knowledge-intensive data positions experienced a structural shift, rising from a baseline of 14.5% to 42.5%, reflecting an enhanced capacity to capitalize on expanding societal demands. At the meso level of practical competence, the award rate in high-level professional competitions increased by 35.4%. At the micro cognitive level, the new evaluation mechanism is associated with a successful redirection of students’ cognitive resources toward algorithmic logic and policy translation (p < 0.001) while highly significantly enhancing their self-efficacy in tackling complex, wicked engineering problems (p < 0.001). Rather than isolating pure causal mechanics, this study interprets these systemic gains as a contextual realignment of academic supply. It provides a context-sensitive, reproducible methodological reference for cultivating professional distinctiveness and reshaping the spatial planning education system in the digital era. Full article

Background: The relationship between the stomatognathic system and postural control has been widely investigated, suggesting that dental occlusion may influence neuromuscular coordination and athletic performance. However, evidence in figure skating remains limited. This study aimed to evaluate the effects of a customized occlusal splint on neuromuscular activity and postural balance in professional figure skaters. Methods: A prospective single-arm pre–post interventional study was conducted on 52 professional female figure skaters (mean age: 17.1 ± 1.7 years). Electromyographic (EMG) activit of the masseter, anterior temporalis, sternocleidomastoid, and trapezius muscles, along with kinesiographic parameters, were assessed at baseline and after six months of continuous occlusal splint use. Postural control was evaluated using the Flamingo Balance Test under three testing conditions. Statistical analysis included paired tests with a significance level set at p < 0.05. Results: After six months of splint therapy, a significant increase in EMG activity of the masseter and anterior temporalis muscles was observed in most participants, along with a reduction in muscular asymmetries. Improvement in sternocleidomastoid and trapezius activity was noted in a subset of subjects. All participants showed correction of mandibular retrusion. Postural performance significantly improved, with enhanced ability to maintain balance during the Flamingo Balance Test. No major adverse effects were reported. Conclusions: Within the limitations of this uncontrolled prospective single-arm study, customized occlusal splint use was associated with changes in neuromuscular activity and postural balance parameters in professional figure skaters. However, causal relationships cannot be established, and randomized controlled studies are required to confirm the efficacy of this intervention. Full article

Background: Ibandronate is a nitrogen-containing bisphosphonate used in osteoporosis; however, its relationship with vertebral-fracture-related outcomes, pain trajectories, and broader inflammatory–skeletal signaling remains incompletely characterized. Methods: This retrospective observational study included patients with osteoporosis categorized according to ibandronate exposure. The primary outcome was new vertebral fracture occurrence, and the secondary outcome was change in pain severity assessed using the Visual Analog Scale (VAS). Multivariable regression, sensitivity analyses, and exploratory network-pharmacology, transcriptomic, and molecular docking analyses were performed. Results: Forty patients (20 ibandronate, 20 control) were included. Ibandronate use was associated with numerically lower vertebral fracture occurrence, although this did not reach statistical significance in crude or adjusted analyses. Greater pain reduction was observed in unadjusted analyses but was attenuated after multivariable adjustment, and baseline heterogeneity should be considered when interpreting between-group differences. Radiological outcomes did not differ significantly between groups. Exploratory systems-level analyses identified enrichment patterns involving inflammatory signaling, osteoclast differentiation, cytokine-associated pathways, and skeletal regulatory processes; however, these findings should be interpreted as hypothesis-generating and not as evidence of causal biological mechanisms. Conclusions: In this exploratory, hypothesis-generating study, ibandronate use was associated with trends toward lower vertebral fracture occurrence and greater unadjusted pain improvement, although these findings were attenuated after adjustment. The combined clinical, transcriptomic, and computational observations are compatible with the possibility that inflammatory and skeletal regulatory pathways may intersect within a broader systems-level framework relevant to vertebral-fracture-related outcomes in osteoporosis. However, these findings should not be interpreted as direct mechanistic evidence of ibandronate-specific molecular activity or clinical efficacy. Larger prospective studies integrating clinical, radiological, and mechanistic approaches are required to clarify the biological and clinical relevance of these observations. Full article

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a common dose-limiting toxicity that disrupts on-time, full-dose chemotherapy, yet no pharmacologic therapy is formally approved. Growing evidence from randomized and late-phase studies with thrombopoietin receptor agonists (TPO-RAs) has renewed interest in targeted supportive care. We evaluated the effectiveness and safety of eltrombopag for CIT in routine clinical practice. Methods: We conducted a small, retrospective, single-arm multicenter cohort study of 31 adults with solid tumors (74.2% stage IV). Given the descriptive, hypothesis-generating nature of this study, no causal inference regarding efficacy can be drawn. Platelet counts and chemotherapy continuity were tracked from baseline through week 12 after eltrombopag initiation. Bleeding, thrombosis, and laboratory safety signals were recorded. Results: The median platelet count increased from 33 × 10⁹/L at baseline to 71 × 10⁹/L at week 1 and 99.5 × 10⁹/L by week 12. Overall, 18/31 patients (58.1%) resumed chemotherapy within 3 weeks, and 15/31 (48.4%) completed planned regimens by week 6. Adverse events were limited to mild, transient elevations in transaminases (n = 3); no major bleeding or thrombotic events occurred. Conclusions: In this real-world multicenter cohort, eltrombopag was associated with rapid platelet recovery and improved chemotherapy deliverability with an acceptable safety profile. The retrospective, single-arm design and the hypothesis-generating nature of these findings preclude definitive conclusions regarding causal efficacy. These observational data highlight the need for prospective controlled trials to characterize the clinical role, optimal dosing, and long-term safety of oral TPO-RAs in CIT. Full article

Background and Objectives: Comprehensive real-world data on dose-adjusted EPOCH-R (DA-EPOCH-R) incorporating molecular prognostic stratification remain limited. We evaluated the long-term efficacy, safety, and prognostic determinants of DA-EPOCH-R in a multicenter Turkish cohort. Materials and Methods: This retrospective study included 140 patients with aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], n = 81; primary mediastinal B-cell lymphoma [PMBL], n = 39; other, n = 20) treated with DA-EPOCH-R at five academic centers (2015–2020). Molecular profiling included immunohistochemistry (MYC, BCL-2, BCL-6) and fluorescence in situ hybridization (FISH). Survival was estimated by Kaplan–Meier analysis with Cox regression for prognostic factors. Results: At a median follow-up of 50.1 months, 5-year overall survival (OS) and event-free survival (EFS) rates were 71.3% and 66.3%, respectively (complete response rate: 68.6%). Molecular subtypes included double-expressor (DEL; n = 39), triple-expressor (TEL; n = 21), double-hit (DHL; n = 17), and triple-hit lymphoma (THL; n = 11). Five-year OS by IPI risk group ranged from 88.6% (low) to 49.4% (high) (p = 0.005). DEL status did not confer inferior OS (p = 0.738), whereas DHL and THL had markedly poor outcomes (p < 0.001). In multivariate analysis, IPI ≥ 3 (HR 2.54; p = 0.007) and MYC FISH rearrangement (HR 3.62; p < 0.001) independently predicted inferior OS. Grade 3–4 neutropenia occurred in 57.1%, with no grade 3–4 cardiotoxicity. Conclusions: DA-EPOCH-R provides favorable long-term outcomes in aggressive B-cell lymphomas. DEL status did not confer a survival disadvantage, an association that is hypothesis-generating and requires confirmation, as the present design cannot establish a causal mechanism. FISH-defined DHL/THL remain associated with dismal outcomes, warranting novel therapeutic strategies. Full article

Background/Objectives: Temporomandibular disorder (TMD) affects a third of the adult population and has been associated with otologic symptoms. These symptoms are frequently misattributed to primary otologic diseases, leading to delays in diagnosis and treatment. This review aims to summarize the reported prevalence, proposed pathophysiologic mechanisms, and management strategies of otologic manifestations in patients with TMD. Methods: A literature review was conducted using the MeSH terms “temporomandibular joint disease” and “otologic symptoms.” Five additional searches were performed using “temporomandibular disease/dysfunction” combined with each of the five most common otologic symptoms. Meta-analyses, randomized controlled trials, reviews, and systematic reviews were prioritized, with preference for studies published within the last 10 years. Inclusion criteria focused on human studies addressing the etiology, clinical presentation, and management of otologic symptoms in TMD populations. Results: The literature supports an association between TMD and otologic symptoms in the absence of primary ear disease. The most commonly described symptoms were aural fullness, otalgia, tinnitus, vertigo, and hearing loss. Conservative approaches, including occlusal splints, physical therapy, behavioral modification, and pharmacologic therapy, demonstrated partial or complete symptom resolution after management of underlying TMD. Conclusions: The literature demonstrates a consistent association between otologic symptoms and TMD, although the underlying mechanisms remain incompletely understood. While conservative TMD management may improve symptoms, exact mechanisms remain unproven. Clinicians should consider TMD in the differential diagnosis when patients present with unexplained otologic complaints. Further research is necessary to establish causality, confirm the efficacy of management protocols, and improve diagnostic accuracy in this overlapping domain. Full article

Background/Objectives: Adolescent suicidal ideation and non-suicidal self-injury (NSSI) are major public health concerns, yet differences between active interventions are often modest. This retrospective study provides preliminary descriptive evidence regarding short-term symptom change across two school-based intervention pathways—Sandplay Therapy with Suicidal ideation and Self-injury Focused Engagement (SPT-SAFE) and a Dialectical Behavior Therapy-informed Brief Intervention (DBT-BI)—in a clinical sample of middle- and high-school adolescents with suicidal ideation and NSSI. Methods: Archival clinical records from 112 adolescents treated in a school-based suicide prevention center were analyzed retrospectively. The sample included 52 adolescents who received SPT-SAFE and 60 who received DBT-BI. Outcomes included suicidal ideation, NSSI frequency, depressive symptoms, anxiety, aggression, impulsiveness, and self-concept. Pre–post changes were examined using mixed-design ANOVAs, with baseline-adjusted ANCOVAs conducted as supplementary analyses. Given the retrospective and clinically assigned design, findings were interpreted as observational associations rather than causal treatment effects. Results: Both intervention groups showed significant pre–post improvements across multiple outcome domains. Overall between-group differences were limited. A nominal, uncorrected Group × Time interaction was observed for impulsiveness, with the DBT-BI group showing a descriptively larger pre–post decrease than the SPT-SAFE group. However, this effect was small and did not remain statistically significant after Bonferroni correction or Benjamini–Hochberg false discovery rate correction across the seven interaction tests. No other outcome showed a multiplicity-adjusted Group × Time interaction. Conclusions: The present study did not provide robust multiplicity-adjusted evidence for differential treatment effects between SPT-SAFE and DBT-BI. The nominal impulsivity finding should be interpreted only as a small, uncorrected exploratory signal for future hypothesis generation. The contribution of this study is therefore descriptive and preliminary, characterizing short-term symptom change in a treatment-engaged adolescent completer sample within a routine school-based service system, rather than supporting domain-specific comparative efficacy or domain-sensitive intervention planning. Full article

Objectives: This systematic review identifies and synthesizes quantitative evidence regarding whether psychosocial constructs, specifically groupness, social support, self-efficacy, enjoyment, and instructor behavior, are associated with behavioral adherence to adult group fitness classes. Methods: Electronic searches were conducted in PubMed, Scopus, and Web of Science. Eligible studies included quantitative analyses of adults in instructor-led group exercise. Risk of bias was appraised using ROBINS-I, and JBI critical appraisal tools, as appropriate to study design. Results: Twenty-one studies met inclusion criteria. Self-efficacy was the most consistently supported domain, with several behavior-specific efficacy measures showing small-to-moderate positive associations with attendance-based adherence, although null findings were also observed when measures were less temporally aligned or when outcomes shifted to post-program continuation. Social-relational and instructor-related constructs showed more context-dependent evidence: social attraction, social cohesion, reliable alliance, group identification, and selected leader behaviors were more consistently favorable than generic social support or broad cohesion measures. Enjoyment and affective response showed the weakest independent evidence, with positive associations mainly when affective constructs were measured close to the attendance decision. Adherence in instructor-led group exercise settings appears to be influenced by perceived capability, social-relational processes, instructor-shaped motivational climate, and affective valuation, although the available evidence is heterogeneous and predominantly observational. Future research should use multilevel longitudinal designs, instructor- and class-level clustering, repeated affective assessment, and causal pathway modeling to test how these mechanisms support repeated attendance and longer-term maintenance. Full article

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4–22%, CBD 2–22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1–5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T² provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan–Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS −5.36 (95% CI −5.65, −5.07), ODI −17.68 (95% CI −19.73, −15.63), BPI-S −6.73 (95% CI −6.99, −6.47), and BPI-I −3.41 (95% CI −3.65, −3.16); all four contrasts had |z| ≥ 16.9 and p < 10⁻²⁰. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T² was F(4, 232) = 872.8, p < 10⁻²⁰. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10⁻⁶⁹), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = −0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05–1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022–2024, with patients returning to in-person follow-up by Year 4–5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54–0.60; BWV AUC 0.51). Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile—ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden—supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials. Full article

The increasing resistance of mosquito vectors to synthetic insecticides poses a major challenge to vector control and global public health, underscoring the urgent need for sustainable, environmentally safe alternatives. This study evaluated the larvicidal activity of aqueous, ethanolic, methanolic, and hydroethanolic extracts of Calotropis procera (Aiton) W.T.Aiton leaves against Aedes aegypti larvae. Significant variations in activity were observed across extraction solvent, ecological zone, and harvest season, with hydroethanolic extracts—particularly those collected in Kombissiri during the dry season—exhibiting the lowest LC₅₀ values among the tested extracts (LC₅₀ < 1600 ppm), indicating moderate larvicidal activity. Phytochemical profiling by high-performance thin-layer chromatography (HPTLC) revealed the presence of several classes of secondary metabolites, including flavonoids, phenolic compounds, tannins, sterols/triterpenes, saponins, coumarins, alkaloids, and cardenolides. Correlation analysis revealed strong negative correlations between larvicidal activity and the concentrations of flavonoids and phenolic compounds, suggesting that higher levels of these metabolites are associated with increased larvicidal effectiveness and may contribute to the observed bioactivity, although these associations remain correlative and do not establish direct causality. These findings highlight the potential of C. procera as a source of plant-based larvicides and demonstrate the influence of environmental factors on their efficacy. From an environmental health perspective, such plant-derived solutions could provide preliminary data for the future optimization of sustainable vector control strategies, while reducing ecological impact and reliance on synthetic insecticides. Full article

The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut–X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota–BA–host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut–heart, gut–kidney, gut–liver, gut–bone, and gut–endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM’s benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota–BA–organ axis thus provides a potential framework for understanding TCM’s systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM’s ecological modulation strategies. Full article

Background/Objectives: Fixed orthodontic appliances interfere with oral hygiene and contribute to plaque retention, gingival inflammation and demineralization of enamel. Standard techniques for keeping oral hygiene (tooth brushing, mouthwashes, dental floss, interdental brush, etc.) are not sufficiently effective. The aim of this study was to investigate the effectiveness, safety, tolerability, and influence on quality of life of an electrolysis device being added to standard techniques of oral hygiene in orthodontic patients, compared to standard methods only. Methods: This 6-month study was designed as an observational prospective-cohort investigation. Primary outcomes of the study were indices of gingival inflammation and bleeding, dental plaque indices, the number of white spots on enamel, and safety (incidence of adverse events). Secondary outcomes were quality of life and overall costs of keeping oral hygiene. Results: The addition of the Neo Pill device to standard oral hygiene maintenance measures was associated with improvements in oral health indices after 6 months; however, given the non-randomized, preference-driven design, these findings reflect an association and should not be interpreted as evidence of causal efficacy. After 6 months, the primary outcomes of the study were significantly reduced compared to the application of only standard oral hygiene methods (from 21 to 55% reduction); the quality of life related to oral health was higher (for 14%), the tolerability of maintaining oral hygiene was the same as with standard measures and the costs of maintaining oral hygiene consumables were lower in the Neo Pill group (median difference 30%); however, this figure excludes the acquisition cost of the device itself, which was donated to all participants by the manufacturer, and the 95% confidence interval for this difference includes zero. Conclusions: The addition of an electrolysis device to standard oral hygiene maintenance measures in people wearing fixed orthodontic appliances was associated with improvements in gingival inflammation, papillary bleeding, and dental plaque indices—outcomes measured with established clinical instruments. Apparent reductions in white-spot lesion counts were also observed but should be considered exploratory given the absence of calibrated or blinded lesion assessment. These findings are preliminary and do not establish causal efficacy. Full article

Background: The gut microbiota constitutes a metabolically active “second genome” that profoundly modulates drug pharmacokinetics, pharmacodynamics, and adverse reaction profiles. Beyond antibiotics, widely prescribed non-antibiotic pharmacotherapies exert clinically relevant pharmacomicrobiomic effects with implications for therapeutic optimisation and pharmacovigilance. Methods: This narrative review, conducted following PRISMA 2020 reporting principles (without PROSPERO pre-registration), searched PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library (January 2015–December 2024) for evidence on proton pump inhibitors (PPIs), metformin, NSAIDs, statins, SGLT2 inhibitors, and oral iron. Evidence tables included clinical human studies with molecular microbiota characterisation (16S rRNA or shotgun metagenomics), ≥20 participants, and a control arm; preclinical data informed mechanistic synthesis. Results: Of 68 eligible studies, 20 met criteria for the evidence tables. PPIs significantly remodelled gut microbiota composition with enrichment of oral-origin taxa (“oralisation of the gut”), associating with Clostridioides difficile infection and SIBO. Metformin enriched Akkermansia muciniphila and butyrate producers, contributing causally to glycaemic efficacy. NSAIDs compromised barrier integrity, with synergistic dysbiosis under PPI co-prescription. Statins correlated with reduced prevalence of the dysbiotic Bact2 enterotype. SGLT2 inhibitor data remained discordant. Oral iron consistently enriched Enterobacteriaceae at the expense of beneficial commensals. Full article